The majority of microorganisms in natural and biological ecosystems exist as biofilms, allowing them to better tolerate stresses and fluctuating environmental conditions. Dental plaque is a complex biofilm on the tooth surface that is subject to fluctuations in environmental factors in the oral cavity. Furthermore, oral biofilms on supragingival surfaces are in the constant presence of S-IgA antibodies;the principal mediator of host immunity in saliva. Little if any data exist on the influence of host immunity on oral biofilms except with respect to attachment. S-IgA can block adhesins, block cell-cell coadhesion, and interfere with nutrient transport systems. In turn, plaque microorganisms can produce specific IgA1 proteases that can cleave S- IgA1. We hypothesize that these interactions could affect not only initial attachment, but could also have a profound effect on the accumulation phase, and the ultimate architecture of the plaque biofilm. To address these gaps in knowledge we propose the following: Specific Aim 1, examine the effects of S-IgA on attachment, development, architecture and viability of biofilms of pioneer oral streptococci (Streptococcus sanguinis, S. oralis and S. gordonii) using a microplate-based biofilm assay, and by confocal laser scanning microscopy. Examine the effects of S-IgA concentration, and exposure to S-IgA during different developmental stages of biofilm formation on ultimate accumulation, architecture and viability. Specific Aim 2, compare the behavior of IgA1 protease-deficient mutants grown in the presence or absence of S-IgA. Compare the effects of intact S-IgA, purified S-IgA1 and Fab1 fragments derived from cleavage by IgA1 proteases on attachment, development, architecture and viability of biofilms of pioneer oral streptococci. Understanding the interplay of host immunity with oral microorganisms, particularly the pioneer colonizers, is critical to understanding how biofilms are formed and shaped in vivo. These interactions are an important consideration in the design of any immunological intervention, such as a vaccine. An understanding of the role of host immunity on biofilms formation might lead to salivary diagnostics that could predict susceptibility to development of pathogenic biofilms. PUBLIC HEALTH RELEVANCE: Understanding the interplay of host immunity with oral microorganisms, particularly those organisms which are involved in first establishing a plaque biofilm (the pioneer colonizers), is critical to understanding how biofilms are formed and shaped in vivo. These interactions are an important consideration in the design of any immunological intervention, such as a vaccine. An understanding of the role of host immunity on biofilm formation might also lead to salivary diagnostics that could predict susceptibility to development of pathogenic biofilms.